Abstracts

Rationale: Published literature on dosing, efficacy and tolerability of lacosamide (LCM) use in young children remains limited. We reviewed records and report our experience of lacosamide treatment in all infants and children less than 12 years of age.Methods: Following IRB approval, all patients < 12 years old who had been treated with LCM between May 2009 and December 2012 were identified. Medical records were audited for demographics, EEG/MRI, seizure type/frequency, previous/current treatments for seizures, and information regarding treatment with LCM: dosing regimen, efficacy and adverse effects (AEs).Results: 148 patients (76 female), median age 7 years (range 1 month 11 years), were treated with LCM. 127/148 (85.5%) have symptomatic epilepsy. 78.4% have cognitive impairment. Median failed past AED trials 6 (range 1 19). 25% also failed to respond to VNS placement, surgery or ketogenic diet. LCM was added to 0 5 concomitant AEDs (77% 2 AEDs). The mean starting dose was 2.9 (range 0.7 23.3) and max dose 9.7 (range 1.3 35) mg/kg/day. Median duration of LCM treatment 7 (range 1 44) months. 38/144 (26.4%) with follow-up had a 50% reduction of seizures from baseline (mean dose 8.9 mg/kg/day) with 16 (11.1%) seizure free (mean 10 months). 52% continue LCM with mean duration of therapy at last contact of 17 (range 1-44) months. 69/146 (47.3%) reported AEs (at mean dose 9 mg/kg/day) compared to 77/146 (52.7%) without AEs (mean dose 10.2 mg/kg/day). Most commonly reported AEs were sedation (22.6%), ataxia (15.1%), nausea/vomiting (10.3%) and dizziness (9.6%) at mean doses of 6.9, 7.1, 7.2 and 9.7 mg/kg/day respectfully. 61.2% of patients whose LCM was added to an AED with a primary mechanism of voltage-gated Na+ channel (VGSC) blockade reported AEs vs. 35.4% whose LCM was added to non-primary VGSC AEDs (mean LCM dose 9.8 and 9.6 mg/kg/day respectively). Mean LCM dose at report of AEs was similar between the two groups for sedation and nausea/vomiting but lower for ataxia (6.7 vs. 7.8 mg/kg/day) and dizziness (6.7 vs. 9.1 mg/kg/day) in the VGSC group. No significant abnormal lab values were documented. One patient developed generalized spike and slow wave complexes on EEG with worsening seizures following LCM infusion. Three patients reported rash and two reported tachycardia. One reported chest pain and bradycardia, but upon LCM rechallenge to a higher dose did not recur. EKG was not routinely performed. 70 patients discontinued LCM due to insufficient benefit (N=55; 78.6%), AEs (N=10; 14.3%) and for simplification of regimen (N=4; 5.7%). 1 patient died unrelated to LCM treatment.Conclusions: Lacosamide demonstrated efficacy and tolerability in children less than twelve years of age. One in every 4 patients had a 50% improvement in seizure control with approximately one out of 10 patients achieving seizure freedom. A mean starting dose of 3 mg/kg/day to a maintenance dose of up to 10 mg/kg/day was tolerated. AEs were mostly mild to moderate and were observed nearly twice as often when LCM was added to regimens containing an AED with a primary mechanism of VGSC blockade.